University of Dundee

‘Crypts, Organoids and Cancer – the Journey of Wnts’

Event Date: 
Thursday, August 22, 2019 - 13:00 to 14:00
Event Location: 
Small Lecture Theatre: Medical Sciences Institute, SLS
Host: 
Dr Gopal Sapkota
Event Speaker: 
Dr David Virshup
Institution: 
Duke NUS Medical School, Singapore
Event Type: 
Seminar
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David Virshup, MD, is Director of the Program in Cancer and Stem Cell Biology at the Duke-NUS Medical School, and Professor of Pediatrics at Duke University in the USA. His research focusses on signal transduction pathways, with a special interest in Wnt signaling and circadian rhythms.

 

David’s laboratory has made seminal contributions to our understanding of the regulation of Wnt/β-catenin pathways, including the discovery that specific targeting subunits of Protein Phosphatase 2A (PP2A) regulate β-catenin degradation in the Wnt pathway, a finding that led to many studies of how reversible phosphorylation regulates Wnt/β-catenin signalling downstream of the membrane. Because multiple Wnts and Wnt-regulated pathways are aberrantly regulated in cancer, David’s lab has focussed recently on Wnt biogenesis, trying to understand where in the stem cell niche Wnts come from in normal and disease states, and how all Wnts can be targeted therapeutically by drugging a key step in early Wnt biogenesis. This has led to the development of ETC159, a drug that blocks Wnt secretion and which is now in phase 1 clinical trials. Another focus of David’s lab is understanding how casein kinase 1 isoforms regulate circadian rhythms. His lab demonstrated that casein kinase 1 regulates PERIOD proteins in mouse and human cells by controlling their ubiquitin-mediated degradation and nucleocytoplasmic shuttling. His current work in circadian rhythms focuses on a phospho-switch mechanism that regulates the stability of the PER2 protein, a central regulator of clock timing. David’s seminar will appeal to those interested in mechanisms of signal transduction in cell, tissue, animal and disease models, development and drug discovery.

 

David received his B.A. from Beloit College and his M.D. from Johns Hopkins in Baltimore, Maryland, where he also received his specialty training in Pediatrics and Pediatric Hematology/Oncology. He established his research laboratory at the University of Utah in 1990 and moved to Singapore in 2007 to join the newly-established Duke-NUS Medical School. David is a member of the American Society of Clinical Investigation, the Association of American Physicians, and a Fellow of the American Association for the Advancement of Science.

 

Key papers:

• Kabiri Z et al. Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts. Development 2014;141:2206–2215.

• Madan, B. et al., (2015) Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene. DOI: 10.1038/onc.2015.280

• Greicius et al., (2018). PDGFRα+ pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells in vivo. PNAS 545, 201713510–E3181.

• Kabiri et al., (2018) Wnt signaling suppresses MAPK-driven proliferation of intestinal stem cells. Journal of Clinical Investigation128:3806-3812.

• Min Zhou, Jae Kyoung Kim, Gracie Wee Ling Eng, Daniel B. Forger, David M. Virshup. (2015). A Period2 Phosphoswitch Regulates and Temperature Compensates Circadian Period. Molecular Cell 60:77-88.